title: Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy.
abstract: OBJECTIVE
  Risk of distant recurrence (DR) among women with estrogen receptor (ER) -positive early breast cancer is the major determinant of recommendations for or against chemotherapy. It is frequently estimated using the Oncotype DX recurrence score (RS). The PAM50 risk of recurrence (ROR) score provides an alternative approach, which also identifies intrinsic subtypes.
  
  
  METHODS
  mRNA from 1,017 patients with ER-positive primary breast cancer treated with anastrozole or tamoxifen in the ATAC trial was assessed for ROR using the NanoString nCounter. Likelihood ratio (LR) tests and concordance indices (c indices) were used to assess the prognostic information provided beyond that of a clinical treatment score (CTS) by RS, ROR, or IHC4, an index of DR risk derived from immunohistochemical assessment of ER, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki67.
  
  
  RESULTS
  ROR added significant prognostic information beyond CTS in all patients (Δ LR-χ(2) = 33.9; P < .001) and in all four subgroups: node negative, node positive, HER2 negative, and HER2 negative/node negative; more information was added by ROR than by RS. C indices in the HER2-negative/node-negative subgroup were 0.73, 0.76, and 0.78 for CTS, CTS plus RS, and CTS plus ROR, respectively. More patients were scored as high risk and fewer as intermediate risk by ROR than by RS. Relatively similar prognostic information was added by ROR and IHC4 in all patients but more by ROR in the HER2-negative/node-negative group.
  
  
  CONCLUSIONS
  ROR provides more prognostic information in endocrine-treated patients with ER-positive, node-negative disease than RS, with better differentiation of intermediate- and higher-risk groups.
authors.affiliation: Academic Department of Biochemistry, Royal Marsden Hospital, and Breakthrough Breast Cancer Centre, Institute of Cancer Research, London, SW3 6JJ, United Kingdom. mitch.dowsett@icr.ac.uk
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Ivana
authors.initials: I
authors.lastname: Sestak
authors.forename: Elena
authors.initials: E
authors.lastname: Lopez-Knowles
authors.forename: Kalvinder
authors.initials: K
authors.lastname: Sidhu
authors.forename: Anita K
authors.initials: AK
authors.lastname: Dunbier
authors.forename: J Wayne
authors.initials: JW
authors.lastname: Cowens
authors.forename: Sean
authors.initials: S
authors.lastname: Ferree
authors.forename: James
authors.initials: J
authors.lastname: Storhoff
authors.forename: Carl
authors.initials: C
authors.lastname: Schaper
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
mesh_terms: D000077384:Anastrozole; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D009570:Nitriles / Q000627:therapeutic use; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D012306:Risk; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D000077384:Anastrozole; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen; D014230:Triazoles; C508053:ERBB2 protein, human